The invention relates to the production of prefilled syringes for use in medical or veterinary treatment.
Prefilled disposable syringes have gained wide acceptance as a preferred dosage form for administration of medicaments, primarily for reasons of safety and convenience. Most importantly, prefilled syringes minimize handling of a medicament prior to administration, thereby reducing the chance of dosage errors or contamination of the medicament.
Many different types of prefilled disposable syringes have been developed. Most known prefilled syringes include an elongate syringe xe2x80x9ccartridgexe2x80x9d or xe2x80x9cbarrelxe2x80x9d comprising a cylindrical glass or plastic container into which the medicament or a component thereof is prefilled. In some types of prefilled syringe, the barrel forms the body of a syringe, having a mouth which permits attachment to an injection needle, and a movable bottom comprising an elastomeric piston which is acted upon by a plunger to administer the medicament.
One common problem with prefilled disposable syringes is that a dedicated filling and capping line is usually required to fill the medicament into the syringe barrel. This problem has previously been addressed by the invention described in the applicant""s European Patent No. 298,585, which describes a system for producing prefilled syringe barrels on ordinary equipment for filling and capping pharmaceutical vials This patent describes a system whereby the syringe barrel is made shorter and wider than a conventional barrel, so that it has the shape of a standard pharmaceutical vial, and is then filled and capped on standard machinery for filling and capping vials, through which the barrels are conveyed while standing on their bases. Since the pharmaceutical vial is a standardized container which is widely used in the pharmaceutical industry, most pharmaceutical companies have existing vial filling equipment. The equipment need only be modified by the addition of a station for insertion of the rubber piston into the body of the barrel. Therefore, the invention described in the applicant""s prior patent eliminates the need for specialized filling equipment, thereby reducing cost.
Despite the improvements described in the applicant""s above-mentioned European patent, the further disadvantage exists that the relatively squat vial-shaped barrels cannot be used in all types of delivery systems. Some delivery systems, such as syringe pumps and two component systems, may require the use of conventional, elongate barrels which cannot be filled on standard vial-filling equipment. Therefore, it would be advantageous to provide a system which allows the preparation of conventional, elongate prefilled syringe barrels on standard equipment for filling and capping pharmaceutical vials.
A further disadvantage exists in that it is not possible to adequately sterilize the assembled syringe barrel (i.e. with the piston completely inserted in the body) by conventional sterilizing agents, including gamma radiation and sterilizing gases such as ethylene oxide or steam. While gamma radiation would sterilize the assembled barrel, it destroys the elasticity of the rubber and therefore cannot be used. Sterilizing gases cannot adequately contact all surfaces of the piston once it is inserted in the body and therefore cannot be used. It would be desirable to supply a syringe barrel which is at least partially assembled and preferably pre-sterilized so as to allow maximum flexibility during the filling operation.
The above-mentioned disadvantages of the prior art are overcome by the present invention, which provides a system for filling and assembling pharmaceutical delivery devices capable of accommodating barrels of various dimensions including elongate syringe barrels. The system according to the invention also provides for partial pre-assembly of the body and the piston, thereby permitting simultaneous sterilization of the body and piston by a sterilizing gas.
In the system according to the invention, means are provided for stabilizing syringe barrels such that they can be conveyed upright without tipping through equipment for filling and capping pharmaceutical vials. Preferably, the stabilizing means comprises a cylindrical sleeve into which the rimmed end of the body (i.e. the end which receives the piston) is inserted, thereby stably supporting the body against tipping.
The system according to the invention also provides means by which the piston is retained in close proximity to the rimmed end of the body, but slightly separated therefrom to permit access to all surfaces of the piston by a sterilizing gas. Preferably, the piston is retained directly below the rimmed end of the body, and substantially centred therewith, to permit the piston to be inserted into the rimmed end of the body merely by pushing the body and piston together.
Accordingly, in one aspect, the present invention provides An assembly for forming a barrel of a pre-filled syringe, comprising: (a) a syringe body having a generally cylindrical side wall with an inner surface and an outersurface, the sidewall extending between a neck end and a rimmed end; (b) a generally cylindrical elastomeric piston having an upper surface, a side surface adapted to form a hermetic seal with the inner surface of the cylindrical side wall when inserted into the open rimmed end of the syringe body, and a lower surface opposite the upper surface; (c) a generally cylindrical sleeve having a base end and a top end, wherein said syringe body is received inside the top end of the sleeve in a close fit with the rimmed end of the syringe body located intermediate the top end and the base end of the sleeve; and (d) piston support means in contact with the sleeve, said piston support means having a support surface on which the piston is supported with its upper surface spaced from the rimmed end of the syringe body and substantially concentric therewith, such that a gap exists between the upper surface of the piston and the rimmed end of the syringe body, thereby permitting sterilization of the syringe body and the piston by a sterilizing gas.
In another aspect, the present invention provides a method for producing a pre-filled syringe body for a pre-filled syringe, the syringe body comprising a barrel and a piston, the barrel having a generally cylindrical side wall with an inner surface and an outer surface, the side wall extending between a neck end and a rimmed end of the barrel, the piston being generally cylindrical and formed of an elastomeric material with an upper surface, a side surface adapted to form a hermetic seal with the inner surface of the barrel when inserted into the open rimmed end of the barrel, and a lower surface opposite the upper surface, the method comprising: (a) forming a first assembly comprising said elastomeric piston, a generally cylindrical sleeve having an inner surface, and outer surface, a base end and a top end, and piston support means in contact with the sleeve and having a piston support surface on which the piston is supported with its lower surface engaging the piston support surface, the piston support surface being spaced radially inwardly of the inner surface of the sleeve; (b) forming a second assembly by inserting the rimmed end of the barrel into the top end of the sleeve to a sufficient depth that the barrel is stably supported in the sleeve, and such that the rimmed end is located intermediate the top end and the base end of the sleeve with a gap between the upper surface of the piston and the rimmed end of the barrel; (c) sterilizing the second assembly with a sterilizing gas; (d) applying a force to the second assembly to cause relative movement of the barrel toward the base end of the sleeve, causing insertion of the piston into the barrel such that the side surface of the piston forms a hermetic seal with the inner surface of the barrel and seals the rimmed end of the barrel; (e) filling said barrel with a medicament or a component thereof through the neck end using equipment for filling and capping pharmaceutical vials; and (f) capping the neck end of the barrel using said equipment for filling and capping pharmaceutical vials; wherein, subsequent to insertion of the piston in step (d), said second assembly is conveyed through at least a portion of said equipment for filling and capping pharmaceutical vials while freestanding in an upright position.